Microfluidic analytical systems are being looked to more and more as a viable means for meeting to the desire to increase throughput, decrease costs, improve automation, and improve data quality in the analysis of chemical and biochemical systems. In many cases, the promise of microfluidics to accomplish many of these goals has been met through the massive parallelization of miniaturized conventional technologies. While providing many benefits over the conventional technologies, the simpler massively parallel systems result in only incremental improvements over conventional technologies, e.g., by a factor of the number of parallel channels. In particular, while removing some of the limitations of conventional technologies, these simpler microfluidic systems do not remove them all. Thus, these systems typically make a minor improvement over conventional systems, e.g., costs, only to run into a further limitation that the microfluidic system doesn't solve, e.g., concurrent control of parallel systems.
Commonly owned Published International Application No. 98/00231 describes methods and systems that address some of these concerns. In particular, assay methods are described that screen test compounds, e.g., pharmaceutical library compounds, in series to determine whether any of these compounds have a desired effect on a given biological system. By screening the compounds in series in a single microfluidic channel network, control of the system is simplified, while still yielding the relatively high serial throughput. Additionally, the throughput is further increased when the system is parallelized, e.g., by providing multiple separate channel networks in which multiple compounds are serially screened.
In serialized systems, however, difficulties can arise in attempting to maximize throughput. In particular, optimizing throughput requires minimizing space between serially introduced compounds within the system. However, a number of factors, e.g., diffusion, electrophoretic biasing, dispersion of fluid materials, etc., weigh against the minimization of the space between adjacent serially introduced compounds. In particular, because fluid samples will diffuse, disperse, and be electrophoretically biased, or smeared, it has typically required that substantial space be given to each fluid volume, in order to avoid intermixing of fluid materials that are introduced in succession. The more space that is required between test compounds, the more time it will take to screen multiple compounds. Further, such dispersion can result in excessive dilution of fluid materials within microscale channels. Due to the extremely small dimensions of microfluidic systems, one generally begins a microfluidic analysis with substantially less material than in conventional analyses, one often cannot afford to have such a dilution occur.
Despite this, it would generally be desirable to provide microfluidic systems, methods of using these systems and methods of designing these systems, which systems are capable of maximizing throughput by permitting materials to be introduced serially, with a minimum amount of space between them. The present invention meets these and a variety of other needs.